HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 44, 46065-46072, October 29, 2004

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 279/44/46065    most recent M403046200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bánfi, B. Articles by Krause, K.-H. Search for Related Content PubMed PubMed Citation Articles by Bánfi, B. Articles by Krause, K.-H. Social Bookmarking                      What's this?

NOX3, a Superoxide-generating NADPH Oxidase of the Inner Ear^*

Botond Bánfi¶, Brigitte Malgrange||, Judit Knisz, Klaus Steger**, Michel Dubois-Dauphin, and Karl-Heinz Krause

From the Department of Anatomy and Cell Biology and Inflammation Program and Dept. of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, ^||Center for Cellular and Molecular Neuroscience, University of Liège, 4020 Liège, Belgium. ^**Institute of Veterinary Anatomy, 35392 Giessen, Germany, and Biology of Ageing Laboratory, Department of Geriatrics, Geneva University Hospitals, 1225 Geneva, Switzerland

Reactive oxygen species (ROS) play a major role in drug-, noise-, and age-dependent hearing loss, but the source of ROS in the inner ear remains largely unknown. Herein, we demonstrate that NADPH oxidase (NOX) 3, a member of the NOX/dual domain oxidase family of NADPH oxidases, is highly expressed in specific portions of the inner ear. As assessed by real-time PCR, NOX3 mRNA expression in the inner ear is at least 50-fold higher than in any other tissues where its expression has been observed (e.g. fetal kidney, brain, skull). Microdissection and in situ hybridization studies demonstrated that NOX3 is localized to the vestibular and cochlear sensory epithelia and to the spiral ganglions. Transfection of human embryonic kidney 293 cells with NOX3 revealed that it generates low levels of ROS on its own but produces high levels of ROS upon co-expression with cytoplasmic NOX subunits. NOX3-dependent superoxide production required a stimulus in the absence of subunits and upon co-expression with phagocyte NADPH oxidase subunits p47^phox and p67^phox, but it was stimulus-independent upon co-expression with colon NADPH oxidase subunits NOX organizer 1 and NOX activator 1. Pre-incubation of NOX3-transfected human embryonic kidney 293 cells with the ototoxic drug cisplatin markedly enhanced superoxide production, in both the presence and the absence of subunits. Our data suggest that NOX3 is a relevant source of ROS generation in the cochlear and vestibular systems and that NOX3-dependent ROS generation might contribute to hearing loss and balance problems in response to ototoxic drugs.

Received for publication, March 18, 2004 , and in revised form, August 13, 2004.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY573239 (rat NOX3) and AY573240 (mouse NOX3).

^* This research was supported by Swiss National Foundation Grant 31-055805.98, by Louis-Jeantet Foundation of Medicine (Geneva), and by Grants AI20866-18 and AG19519-01 from the National Institutes of Health, United States Public Health Service. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1S.

^¶ To whom correspondence should be addressed: Department of Anatomy and Cell Biology, University of Iowa, D186 MTF, 2501 Crosspark Road, Coralville, IA 52241. Tel.: 319-335-4228; Fax: 319-335-4194; E-mail: botond-banfi{at}uiowa.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Q. Zhang, P. Malik, D. Pandey, S. Gupta, D. Jagnandan, E. B. de Chantemele, B. Banfi, M. B. Marrero, R. D. Rudic, D. W. Stepp, et al. Paradoxical Activation of Endothelial Nitric Oxide Synthase by NADPH Oxidase Arterioscler. Thromb. Vasc. Biol., September 1, 2008; 28(9): 1627 - 1633. [Abstract] [Full Text] [PDF]

				S. L. Cassel, S. C. Eisenbarth, S. S. Iyer, J. J. Sadler, O. R. Colegio, L. A. Tephly, A. B. Carter, P. B. Rothman, R. A. Flavell, and F. S. Sutterwala The Nalp3 inflammasome is essential for the development of silicosis PNAS, July 1, 2008; 105(26): 9035 - 9040. [Abstract] [Full Text] [PDF]

				A. Orient, A. Donko, A. Szabo, T. L. Leto, and M. Geiszt Novel sources of reactive oxygen species in the human body Nephrol. Dial. Transplant., May 1, 2007; 22(5): 1281 - 1288. [Full Text] [PDF]

				D. Jagnandan, J. E. Church, B. Banfi, D. J. Stuehr, M. B. Marrero, and D. J. R. Fulton Novel Mechanism of Activation of NADPH Oxidase 5: CALCIUM SENSITIZATION VIA PHOSPHORYLATION J. Biol. Chem., March 2, 2007; 282(9): 6494 - 6507. [Abstract] [Full Text] [PDF]

				P. Moskwa, D. Lorentzen, K. J. D. A. Excoffon, J. Zabner, P. B. McCray Jr., W. M. Nauseef, C. Dupuy, and B. Banfi A Novel Host Defense System of Airways Is Defective in Cystic Fibrosis Am. J. Respir. Crit. Care Med., January 15, 2007; 175(2): 174 - 183. [Abstract] [Full Text] [PDF]

				K. Bedard and K.-H. Krause The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology Physiol Rev, January 1, 2007; 87(1): 245 - 313. [Abstract] [Full Text] [PDF]

				M. Geiszt NADPH oxidases: New kids on the block Cardiovasc Res, July 15, 2006; 71(2): 289 - 299. [Abstract] [Full Text] [PDF]

				P. L. Hordijk Regulation of NADPH Oxidases: The Role of Rac Proteins Circ. Res., March 3, 2006; 98(4): 453 - 462. [Abstract] [Full Text] [PDF]

				T. Ueyama, M. Geiszt, and T. L. Leto Involvement of rac1 in activation of multicomponent nox1- and nox3-based NADPH oxidases. Mol. Cell. Biol., March 1, 2006; 26(6): 2160 - 2174. [Abstract] [Full Text] [PDF]

				T. Kawahara, D. Ritsick, G. Cheng, and J. D. Lambeth Point Mutations in the Proline-rich Region of p22phox Are Dominant Inhibitors of Nox1- and Nox2-dependent Reactive Oxygen Generation J. Biol. Chem., September 9, 2005; 280(36): 31859 - 31869. [Abstract] [Full Text] [PDF]

				N. Ueno, R. Takeya, K. Miyano, H. Kikuchi, and H. Sumimoto The NADPH Oxidase Nox3 Constitutively Produces Superoxide in a p22phox-dependent Manner: ITS REGULATION BY OXIDASE ORGANIZERS AND ACTIVATORS J. Biol. Chem., June 17, 2005; 280(24): 23328 - 23339. [Abstract] [Full Text] [PDF]

				B. J. Goldstein, K. Mahadev, and X. Wu Redox Paradox: Insulin Action Is Facilitated by Insulin-Stimulated Reactive Oxygen Species With Multiple Potential Signaling Targets Diabetes, February 1, 2005; 54(2): 311 - 321. [Abstract] [Full Text] [PDF]